TY - JOUR T1 - Discovery of 1-((6-Aminopyridin-3-yl)Methyl)-3-(4-Bromophenyl)Urea as a Potent, Irreversible Myeloperoxidase Inhibitor JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 147 LP - 154 DO - 10.1124/jpet.118.248435 VL - 367 IS - 1 AU - Martin L. Marro AU - Andrew W. Patterson AU - Lac Lee AU - Lin Deng AU - Aimee Reynolds AU - Xianglin Ren AU - Laura Axford AU - Anup Patnaik AU - Micah Hollis-Symynkywicz AU - Nigel Casson AU - Dominique Custeau AU - Lisa Ames AU - Sally Loi AU - Lihe Zhang AU - Toshiyuki Honda AU - Jutta Blank AU - Tyler J. Harrison AU - Julien P. N. Papillon AU - Lawrence G. Hamann AU - Jovita Marcinkeviciene AU - Jean B. Regard Y1 - 2018/10/01 UR - http://jpet.aspetjournals.org/content/367/1/147.abstract N2 - Myeloperoxidase (MPO) is a leukocyte-derived redox enzyme that has been linked to oxidative stress and damage in many inflammatory states, including cardiovascular disease. We have discovered aminopyridines that are potent mechanism-based inhibitors of MPO, with significant selectivity over the closely related thyroid peroxidase. 1-((6-Aminopyridin-3-yl)methyl)-3-(4-bromophenyl)urea (Aminopyridine 2) inhibited MPO in human plasma and blocked MPO-dependent vasomotor dysfunction ex vivo in rat aortic rings. Aminopyridine 2 also showed high oral bioavailability and inhibited MPO activity in vivo in a mouse model of peritonitis. Aminopyridine 2 could effectively be administered as a food admixture, making it an important tool for assessing the relative importance of MPO in preclinical models of chronic inflammatory disease. ER -